Patients with cancer who are treated with surgery and adjunctive chemotherapy often have improved survival, yet they remain at risk for disabling functional decline. Cancer, like other chronic diseases affecting the aged, is associated with neuropsychological and physiological changes that likely contribute to this decline. However, this hypothesis has not been tested with longitudinal observation. Moreover, executive function, which is strongly associated with functional impairment in multivariable models, is rarely assessed in populations with cancer. No longitudinal studies have utilized neuroimaging to extend our understanding of the critical brain regions associated with functional decline. Longitudinal studies incorporating multidimensional neuropsychological assessment, neuroimaging, and serum biomarkers are needed to understand how cognition, cerebral metabolism, and physiological changes interact to precipitate functional decline in cancer survivors. The purpose of this application is to describe the one-year postsurgical change in lADL functional status and neuropsychological performance observed in non-demented elders with colon cancer referred for adjuvant chemotherapy compared to a cancer-free elder control group. We will identify the neuropsychological domains associated with functional decline in elders with colon cancer during the one-year postsurgical period. We will determine the association between post chemotherapy cerebral glucose metabolism as measured with resting fluorodeoxyglucose positron emission tomography (FDG-PET) and functional status in nondepressed colon cancer survivors. Finally, we will explore the relationship between serum biomarkers for physiological changes associated with cancer (interleukin 1, interleukin 6, hemoglobin, and albumin) and functional and cognitive decline. RELEVANCE: This study will be the first to describe longitudinal change in functional status, neuropsychological performance, and serum biomarkers for frailty across multiple methods of assessment in elder cancer survivors. It will also be the first to establish FDG-PET neuroimaging as a biomarker for functional status in elder cancer survivors. This project will inform future intervention studies that target the neuropsychological impairments and physiological changes mediating functional decline in colon cancer survivors.